Succinate dehydrogenase [ubiquinone] iron-sulfur subunit, mitochondrial (SDHB)

Succinate dehydrogenase [ubiquinone] iron-sulfur subunit, mitochondrial (SDHB), is one of four subunits comprising the succinate dehydrogenase (SDH, complex II) enzyme complex of the mitochondrial inner membrane, which links the citric acid (Krebs) cycle and the electron transport chain[1][3][5][6]. SDHB is an iron-sulfur protein responsible for receiving electrons from SDHA-bound flavin adenine dinucleotide (FADH2) and shuttling them through three iron-sulfur clusters ([2Fe-2S], [4Fe-4S], [3Fe-4S]) to ubiquinone, contributing to ATP production by oxidative phosphorylation[1][2][5]. The SDHB gene is nuclear-encoded and acts as a tumor suppressor; mutations in SDHB increase risk for hereditary paraganglioma, pheochromocytoma, gastrointestinal stromal tumors (GISTs), and are implicated in diverse mitochondrial and neurodegenerative diseases[1][3][4][5]. Loss of SDHB protein can be detected immunohistochemically and is used as a biomarker for SDH-deficient tumors[5]. Dysfunctional SDHB leads to succinate accumulation, stabilization of hypoxia-inducible factors (HIFs), abnormal angiogenesis, disrupted cellular metabolism, and cancer predisposition[3][5]. Direct pharmacological targeting is limited, but SDHB is considered a therapeutic target in metabolic, oncologic, and mitochondrial research.

Other names

Succinate dehydrogenase complex iron sulfur subunit BIron-sulfur subunit of complex IISuccinate dehydrogenase [ubiquinone] iron-sulfur subunit, mitochondrialIpMalate dehydrogenase [quinone] iron-sulfur subunitCWS2MC2DN4PGL4PPGL4SDHSDH1SDH2SDHIP

Enzyme inhibition (experimental: inhibiting SDH leads to succinate accumulation and altered redox states); Indirect modulation (research: targeting metabolic pathways/disrupting pseudohypoxia signaling in SDH-deficient tumors)